Aggressive peripheral T‐cell lymphoma containing Epstein–Barr virus genomes

A 42‐year‐old woman presented in December 1995 with a half‐year history of asymptomatic erythematous plaques with firm induration on her extremities (Fig. 1). In the biopsy specimen, they were composed of medium‐ to large‐sized pleomorphic lymphoid cells with nuclear atypia and frequent mitoses, which extensively infiltrated the dermis and subcutis (Fig. 2a). There were also large phagocytic cells filled with nuclear dusts and erythrocytes (Fig. 2b). Immunohistochemlcal staining performed on paraffin‐embedded sections using the labeled streptavidine‐biotin‐immunoperoxidase technique revealed that the atypical lymphoid cells were positive for CD3, a T‐cell marker, but negative for CD20, a B‐cell marker. Large phagocytic cells were positively stained with PGM1, a macrophage marker. Unfortunately, we could not obtain further information concerning the gene rearrangement or immunostaining of the T‐cell receptor because only paraffin‐fixed samples were available. A complete blood cell count revealed mild thrombocytopenia, but it was otherwise within normal limits. Atypical cells were absent in the peripheral blood and bone marrow. The serum level of lactate dehydrogenase was elevated at 1402 lU/L. Antibodies to human T‐lymphotrophic virus (HTLV–1) were negative. The titers of antibodies to human Epstein‐Barr virus (EBV) were as follows: viral capsid antigen (VCA) IgM type, <10; VCA IgG type, 640; early antigen (EA) IgG, 40; EBV‐determined nuclear antigen (EBNA), 40. Under a diagnosis of T‐cell lymphoma, we suspected the association of the lymphoma cells with EBV infection from the moderately high titers of antibodies to EBV, and performed in situ hybridization for EBV‐encoded nuclear RNAs (EBER). After hybridization, the detection of specifically bound fluorescein (FITC)‐conjugated antisense RNA probes (Dako, Kyoto, Japan) was achieved by anti‐FITC monoclonal antibody conjugated with alkaline phosphatase. More than 90% of lymphoid cells exhibited EBER‐positive nuclei, and almost all of the infiltrating cells in the same area expressed CD3 and CD45RO. No signal was observed for sense RNA probes, and suitable control specimens from EBV‐positive and EBV‐negative cases were used as controls for EBV detection. Together with a rapid exacerbation of the skin tumors, a marked protrusion of the left eye appeared, behind which computed tomographic (CT) scan demonstrated the presence of a mass. CT scan of the abdomen also revealed large masses compatible with lymphoma. The patient was treated with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP). However, the response to this therapeutic regimen was transient with only a brief remission interval, and the patient died of progressive disease 2 months after starting the chemotherapy.